title: Endothelial cell stimulation overcomes restriction and promotes productive and latent HIV-1 infection of resting CD4+ T cells.
abstract: Highly active antiretroviral therapy (HAART) is able to suppress human immunodeficiency virus type 1 (HIV-1) to undetectable levels in the majority of patients, but eradication has not been achieved because latent viral reservoirs persist, particularly in resting CD4(+) T lymphocytes. It is generally understood that HIV-1 does not efficiently infect resting CD4(+) T cells, and latent infection in those cells may arise when infected CD4(+) T lymphoblasts return to resting state. In this study, we found that stimulation by endothelial cells can render resting CD4(+) T cells permissible for direct HIV infection, including both productive and latent infection. These stimulated T cells remain largely phenotypically unactivated and show a lower death rate than activated T cells, which promotes the survival of infected cells. The stimulation by endothelial cells does not involve interleukin 7 (IL-7), IL-15, CCL19, or CCL21. Endothelial cells line the lymphatic vessels in the lymphoid tissues and have frequent interactions with T cells in vivo. Our study proposes a new mechanism for infection of resting CD4(+) T cells in vivo and a new mechanism for latent infection in resting CD4(+) T cells.
authors.affiliation: Department of Biology, Calvin College, Grand Rapids, Michigan, USA. as28@calvin.edu
authors.forename: Anding
authors.initials: A
authors.lastname: Shen
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Baker
authors.forename: Geoffrey L
authors.initials: GL
authors.lastname: Scott
authors.forename: Yelena P
authors.initials: YP
authors.lastname: Davis
authors.forename: Yen-Yi
authors.initials: YY
authors.lastname: Ho
authors.forename: Robert F
authors.initials: RF
authors.lastname: Siliciano
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology*; D060833:Cellular Microenvironment / Q000276:immunology; D054415:Chemokine CCL19 / Q000378:metabolism; D054421:Chemokine CCL21 / Q000378:metabolism; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D008213:Lymphocyte Activation; D017735:Virus Latency / Q000276:immunology*; D014779:Virus Replication / Q000276:immunology
chemical_list: C515460:CCL19 protein, human; C515478:CCL21 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; C569274:IL15 protein, human; C508605:IL7 protein, human; D019409:Interleukin-15; D015851:Interleukin-7